RheumatoidArthritisSH1 Flashcards
Rheumatoid arthritis
Types of meds
Autoimmune
NSAIDs: not to prevent or slow joint destruction. Helps sx. Used in conjunction with DMARDs
Corticosteroids: great bridge therapy until DMARDs start working
- RAYOS ( prednisone ) delayed release formulation that can be taken at night so RA patients can be not as stiff in am and move joints.
DMARDS
Disease modifying anti rheumatic drugs
• NON - biological DMARDS : should be started within 3 months of dx.
Most start with methotrexate or leflunomide ( arava )
If milder RA can start with hydroxychloroquine or another DMARD
Biological DMARDs : saved for patients who dont respond well to non-biologics
Most start with TNF blocker such as Enbrel, Humira, or Remicade. Patients with poor prognosis may get Orencia, Rituxan
Auranofin ( Ridaura )
1 side effect diarrhea
Gold compounds
Methotrexate side effect
M-mucocytosis
E
T
H- hepatic toxicity
☀️- photosensitivity ; bald head ( alopecia )
T
R- RASH/ Renal ( crystal formations can occur in kidneys so) you want to give bicarbonate to keep that urine alkaline
E
X- x-ray bc watch for pulmonary fibrosis ( watch of cough /SOB ) / PREGnancy category X
A
T
E
And check labs on all DMARDS ( CBC ) -monitoring parameters ( •cbc ( WBC and platelets q4wks, • CXR, •LFT 9q3-4 months) , • renal function )
Methotrexate
•Trexall - PO
•Otrexup; Rasuvo : autoinjector • subQ ( preservative free )
MOA:
- antimetabolite chemo ( cell cycle specific )
-S phase toxin ( DNA synthesis phase )
-Folic acid structural analog
-competitively inhibits DHF reductase
-inhibits de novo pyrimidine synthesis:
Dosing is very important: chemo methotrexate very different than RA or psoriasis
Methotrexate indications
ectopic pregnancy ( category X ) ( “off label use “ )
Psoriasis
Cancer chemo
RA
Dosing for methotrexate for RA
Once weekly!
7.5 mg weekly or 2. 5 mg tabs q12 hours x 3 doses given ( Qweek )
Max 20 mg /week
Folate 1mg /day except the day of MTX
Takes 4 to 6 weeks to get full response ( relatively quick ) but patient may need to be on steroids ( bridge therapy ) until it kicks in those 4 to 6 weeks
DMARD
Disease modifying anti rheumatic drugs
- suppress your own immune system form attacking itself
DDI methotrexate
Contraindications
Bactrim , PPI , NSAIDS , levetiracetam : all increase MTX toxicity
Bactrim - hold bactrim or MTX( trimethoprim component affects hydrofolate so you know it causes immunosupression )
PPI: recommend h2 blocker
NSAIDs/ salicylates: caution
Levetiracetam may increase MTX levels
contraindications : preg category X ( use birth control bc males shouldn’t get someone pregnant as well ) ; renal insufficiency ( creatinine > 1.5 ) ; pleural effusion, active stomatitis, diarrhea or infection, immuno-deficiency ; alcochol use or liver disease ( hepatotoxicity ) ; age> 70 ( as you age renal function goes down )
Methotrexate antidote?
Leucovorin
Leflunomide
Arava
MOA: Pyrimidine inhibitor. Inhibits dihydroorotate dehydrogenases. Inhibitor of T cell activation & proliferation. Similar to MTX in effects and efficacy.
Onset of action : 1 to 2 months
Loading dose: 100 mg po QD for 3 days. Maintenance : 10 - 20 mg once daily
SE
L - LFTs, long half life ( could take up to 2 years for serum conc of drug to be undetectable / LIVER labs
A- alopecia / check ALT/AST every month
Diarrhea
Cholestyramine 8 grams TID x 11 days
To get rid of Leflunomide. Wash out procedure
Say patient wants to get pregnant or another reason. ( preg X )
Can also use activated charcoal
Azathiopurine
IMURAN
MOA: purine analog / Antimetabolite converts to 6MP
Azathiopurine and 6MP needs xanatnine oxidase to be metabolized. ( allopurinol xanathine oxidase inhbitor )
If you add allopurinol / febuxostat ( uloric ) : you worry about azathiopurine or 6MP toxicity so decrease dosage of 6MP or imuran
Preg category D
Indication: RA, renal transplantation
Dosing : 100 mg PO qd; 1-2mg/kg/day
Contraindications
Azathioprine
IMURAN
- if it works on s phase so it can cause myelosuppresion.
All DMARDs cause myelosuppresion : check CBC
D-Penicillamine
( cuprimine ) - COPPER
Never first line for RA
Used for RA and can be used Wilson’s disease ( too much copper in system ) / used for lead poisoning.
Penicillins on empty stomach
D-penicillamine on empty stomach
DMARD SE
Myelosuppresion,
GI
Renal
Contraindications : myasthenia gravis,
Hydroxychloroquine
Plaquenil : plaques in my eyes
MOA: antimalarial agent used in RA
Indications; early RA ( off label ) ; malaria
200 -400 mg po QD with food or milk
D/C if no response in 6 months
SE: myopathy, RETINOPATHY ( irreversible retinal damage ) , neurological ( early HA, insomnia, ) late ( tinnitus/ decreased hearing acuity )
Monitoring : baseline eye exam. If long term use yearly eye exams. CBC liver muscle strength
Hydroxychloroquine adverse effects
H
Y
D
R
👀
X
Y
C
H
L
🦻
R
O
Q
U
I
N
E
Sulfasalazine
Azulfidine
Dont fill: if sulfa allergy or salicylates allergy
MOA: 5-ASA is the active component of sulfasalazine
Efficacy 1-3 months
Indications: UC ( ulcerative colitis ) and RA
Dosing RA: 500 mg enteric coated delayed release qd-bid after meals
Increase to 1 gram PO BID
Dosing Ulcerative colitis: much higher. 500 -1000 mg PO QID
Sulfasalazine side effects
Azulfidine
Rash ( Steven Johnson’s syndrome ), HA, GI upset
Myelosuppresion ( check CBC )
Orange - yellow discoloration of skin, lenses and urine,
Fertility impairment
Pregnancy category B
Monitor : CBC, LFT, renal , hypersensitivity reaction
Contraindications : avoid in hepatic and renal failure, sulfonimide or salicylates sensitivity
Tofacitinib
Xeljanz
MOA: JAK inhbitor ( Janus kinases )
Indications: RA patients with low response or intolerant to MTX
Monotherapy, or in combination with MTX other NONBIOLOGIC DMARDs
Dont combine with biological, azathioprine or cyclosporine , or TNF blockers ( major immunosuppression )
DDI : substrate, watch for cyp3a4 (and cyp2C19 inhbitors will increase dose. Cyp3a4 inducer ( RIFAMPIN ) will decrease dose
Adverse effects: D/C if ANC<500. TB: check TB prior
Anakinra
Kineret
MOA: interleukin 1 R antagonists
Indications: RA
Dosing: 100 mg SUBQ once daily ( rotate injection sites
Refrigerate
S/E: its a DMARD so watch for neutropenia , dont use if active infection, dont use with TNF blockers ( etanercept, infliximab,adalimumab, or abatacept
Injection site rash
Headache, vomiting, pulmonary infections ( COPD)
Monitoring : CVC for neutrophil count, TB test at baseline, serum creatinine, infections
Dont use these two medications with TNF blockers bc can cause major immunosuppression
Tofacetinib (xeljanz ) and anakinra ( kineret )
Etanercept
Enbrel; Erelzi ( etanercept-szzs)
Erelzi: biosimilar form of etanercept ( Enbrel )
MOA: TNF receptor blocker
-rapid onset and very effective. Good synergistic effect with MTX
Indications: RA, psoriatic arthritis, juvenile idiopathic arthritis, plaque psoriasis. RA combined with MTX and other DMARDs
Dosing RA: 50 mg subq once weekly ( prefilled syringe )
Refrigerate
SE: potential risk of infection
Monitoring: TB prior, CBC
Allergies: needle cover latex
Contraindications : never give with live vax, never give with anakinra ( kineret ) / dont give with cyclophosphamide
Infliximab
I - IV
Remicade, Inflectra ( biosimilar form but not as interchangeable)
MOA: anti - TNF alpha monoclonal antibody.
Indications: Crohn’s disease, UC, Plaque psoriasis, psoriatic arthritis, refractory RA ( added to MTX or other agents)
Infusion : every 8 weeks 6 times per year. Start infusion within 3 hours of making it ( make in NS )
Contraindications: TB ( check PPD ) , live vax, IL blocker ( Anakinra - major immunosuppression ) , dont give with Xeljanz ( major immuno
All TNF blockers ( Remicade , Enbrel ) can be used for psoriasis
T
ALL TNF blockers can worsen HF
Monitor for CHF
T
Adalimumab
Humira
Amjevita - biosimilar form
SUBQ
MOA: monoclonal Ab. TNF blocker
Indications: RA: alone or with MTX
-psoriatic arthritis ( PsA) in adults
-anklosing spondylitis in adults ( when spine is straight and inflamed )
-Crohn’s disease ***** often used for CD in adults
40 mg SUBQ every other week ( if on MTX ) , if not on MTX then 40 mg SUBQ QW
Refrigerate/ protect from light
Humira adverse effects
Adalimumab TNF blocker
SE: infections, TB, viruses, fungi
- myelosuppresion: bone marrow suppression
-cancer
-HF SOB edema
-LUPUS like syndrome
Contraindications with all TNF blockers : don’t combine with anakinra or tofacitinib ( xeljanz ) - major immunosuppression / avoid live
Monitor: CBC
Golimumab
Simponi SC
Simponi Aria - IV
Indications: RA ( combine with MTX ) , PsA, anklosing spodylitis ( arthritis of spine ) , UC
MOA: targets and neutralizes TNF -alpha
Riding this pony once a month: SUBQ once monthly
Certolizumab
Cimzia
indications: RA, Crohn’s disease, AS, PsA
TNF inhbitor
SE: CHF, infections,
SUBQ
Abatecpet ( orencia ) a lot stronger than TNF
T
When you fail TNF then we can use abatecpt ( orencia ). This is not a TNF blocker
For RA
Abatacept
Orencia
IV and SUBQ
MOA: selective T cell co stimulation modulator ( NOT A TNF blocker )
indication: RA ( for pts who dont respond to MTX, TNF blockers or other DMARDs)
SE: caution with COPD patients ( worry about pulmonary IFX) , immunosuppressants so dont give live vax
Rituximab
Rituxan ( IV infusion ) - must give prophylactic pretreatment with APAP and antihistamine / steroids
Refrigerate
Can be in combo with MTX
MOA: monoclonal AB to the CD20 antigen that depletes CD20 positive B cells
Indications: refractory RA, Non- Hodgkin lymphoma
contraindications: live vax , contraindicated if allergy to Murine proteins
SE: tumor lysis syndrome , hep B, nephrotoxic
Tocilizumab
Actemra - IV once a month/ subQ once a week
MOA: interleukin-6 ( IL 6 ) inhbitor
Precautions: infections, PPD TB test, anaphylaxis, no live VAX, labs: ( dont give if ANC < 2000/ mmˆ3 , platelets < 100,000mmˆ3 or ALT / AST > 1.5 x ULN
Review of NON biological DMARDS
Methotrexate
Leflunomide ( Arava )
Azathioprine ( IMURAN )
D-Penicillamine ( Cuprimine )
Hydroxychloroquine ( plaquenil )
Sulfasalazine ( Azulfidine )
Tofacitinib ( Xeljanz ) Janus kinase ( JAK ) inhbitor
Review of biological agents
IL-1 R antagonists: anakinra ( kineret ) : SC, QD
5 TNF blockers:
• adalimumab ( Humira ) : 40 mg sc every other week
• Etanercept ( Enbrel ) : 50 mg SQ once weekly
• Infliximab ( Remicade ) : IV infusion every 8 weeks
•Golimumab ( Simponi ) QD once a month IV q8weeks
• Certolizumab ( Cimzia ) : SQ once or twice a month
T cell activation inhibitor : • ABATACEPT ( ORENCIA ) IV / SC
CD20 monoclonal antibody : Rituximab ( Rituxan ) IV
Interleukin -6 ( IL-6 ) inhbitor : Tocilizumab ( actemra ) IV /SC
Newer meds
•sarilumab ( Kevzara ) IL -6 like actemra- subq q 2wks. SE like actemra
•Barcitinib ( Olumiant ) : Janus Kinase Inhbitor ( JAK ) - oral
- ppd test
• Upadacitinib ( Rinvoq) : JAK inhibitor - oral
